N-acetyl-cysteine and H. pylori urease activity

2001 ◽  
Vol 120 (5) ◽  
pp. A589-A589
Author(s):  
H HUYNH ◽  
R COUPER ◽  
C TRAN ◽  
A MUHAMED ◽  
R BUTLER
Keyword(s):  
Urease Activity ◽  
Acetyl Cysteine ◽  
H Pylori

N-acetyl-cysteine and H. pylori urease activity

2001 ◽  
Vol 120 (5) ◽  
pp. A589
Author(s):  
Hien Huynh ◽  
Richard Lt Couper ◽  
Cuong Tran ◽  
Azhani Muhamed ◽  
Ross N. Butler
Keyword(s):  
Urease Activity ◽  
Acetyl Cysteine ◽  
H Pylori

scholarly journals Zerumbone Inhibits Helicobacter pylori Urease Activity

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2663
Author(s):  
Hyun Jun Woo ◽  
Ji Yeong Yang ◽  
Pyeongjae Lee ◽  
Jong-Bae Kim ◽  
Sa-Hyun Kim
Keyword(s):  
Helicobacter Pylori ◽  
Carbon Atom ◽  
Natural Compound ◽  
Urease Activity ◽  
Negative Charge ◽  
Positive Charge ◽  
Gastric Epithelium ◽  
Functional Inhibition ◽  
Electrical Gradient ◽  
H Pylori

Helicobacter pylori (H. pylori) produces urease in order to improve its settlement and growth in the human gastric epithelium. Urease inhibitors likely represent potentially powerful therapeutics for treating H. pylori; however, their instability and toxicity have proven problematic in human clinical trials. In this study, we investigate the ability of a natural compound extracted from Zingiber zerumbet Smith, zerumbone, to inhibit the urease activity of H. pylori by formation of urease dimers, trimers, or tetramers. As an oxygen atom possesses stronger electronegativity than the first carbon atom bonded to it, in the zerumbone structure, the neighboring second carbon atom shows a relatively negative charge (δ−) and the next carbon atom shows a positive charge (δ+), sequentially. Due to this electrical gradient, it is possible that H. pylori urease with its negative charges (such as thiol radicals) might bind to the β-position carbon of zerumbone. Our results show that zerumbone dimerized, trimerized, or tetramerized with both H. pylori urease A and urease B molecules, and that this formation of complex inhibited H. pylori urease activity. Although zerumbone did not affect either gene transcription or the protein expression of urease A and urease B, our study demonstrated that zerumbone could effectively dimerize with both urease molecules and caused significant functional inhibition of urease activity. In short, our findings suggest that zerumbone may be an effective H. pylori urease inhibitor that may be suitable for therapeutic use in humans.

scholarly journals The role of acid inhibition in Helicobacter pylori eradication

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1747 ◽  
Author(s):  
David R. Scott ◽  
George Sachs ◽  
Elizabeth A. Marcus
Keyword(s):  
Helicobacter Pylori ◽  
Urease Activity ◽  
Eradication Therapy ◽  
Acid Inhibition ◽  
Acid Suppression ◽  
Helicobacter Pylori Eradication ◽  
Ulcer Disease ◽  
Chronic Active Gastritis ◽  
H Pylori

Infection of the stomach by the gastric pathogen Helicobacter pylori results in chronic active gastritis and leads to the development of gastric and duodenal ulcer disease and gastric adenocarcinoma. Eradication of H. pylori infection improves or resolves the associated pathology. Current treatments of H. pylori infection rely on acid suppression in combination with at least two antibiotics. The role of acid suppression in eradication therapy has been variously attributed to antibacterial activity of proton pump inhibitors directly or through inhibition of urease activity or increased stability and activity of antibiotics. Here we discuss the effect of acid suppression on enhanced replicative capacity of H. pylori to permit the bactericidal activity of growth-dependent antibiotics. The future of eradication therapy will rely on improvement of acid inhibition along with current antibiotics or the development of novel compounds targeting the organism’s ability to survive in acid.

scholarly journals Energetics of Helicobacter pylori and Its Implications for the Mechanism of Urease-Dependent Acid Tolerance at pH 1

2002 ◽  
Vol 184 (11) ◽  
pp. 3053-3060 ◽  
Author(s):  
Kerstin Stingl ◽  
Eva-Maria Uhlemann ◽  
Roland Schmid ◽  
Karlheinz Altendorf ◽  
Evert P. Bakker
Keyword(s):  
Helicobacter Pylori ◽  
Membrane Potential ◽  
Urease Activity ◽  
Cytoplasmic Ph ◽  
Ph Homeostasis ◽  
Intact Cells ◽  
Ph Values ◽  
Cell Extracts ◽  
H Pylori ◽  
External Ph

ABSTRACT In the presence of urea the neutrophilic human pathogen Helicobacter pylori survives for several hours at pH 1 with concomitant cytoplasmic pH homeostasis. To study this effect in detail, the transmembrane proton motive force and cytoplasmic urease activity of H. pylori were determined at various pH values. In the absence of urea, the organism maintained a close-to-neutral cytoplasm and an internally negative membrane potential at external pH values greater than 4 to 5. In the presence of urea, H. pylori accomplished cytoplasmic pH homeostasis down to an external pH of 1.2. At this external pH, the cytoplasmic pH was 4.9 and the membrane potential was slightly negative inside. The latter finding is in contrast to the situation in acidophiles, which develop inside-positive membrane potentials under similar conditions. Measurements of the time course of the membrane potential confirmed that addition of urea to the cells led to hyperpolarization. Most likely, this effect was due to electrogenic export of ammonium cations from the cytoplasm. The urease activity of intact cells increased nearly exponentially with decreasing external pH. This activation was not due to enhanced gene expression at low external pH values. In cell extracts the pH optimum of urease activity was dependent on the buffer system and was about pH 5 in sodium citrate buffer. Since this is the cytoplasmic pH of the cells at pH 1 to 2, we propose that cytoplasmic pH is a factor in the in vivo activation of the urease at low external pH values. The mechanism by which urease activity leads to cytoplasmic pH homeostasis in H. pylori is discussed.

scholarly journals Selection for Urease Activity duringHelicobacter pylori Infection of Rhesus Macaques (Macaca mulatta)

2001 ◽  
Vol 69 (5) ◽  
pp. 3519-3522 ◽  
Author(s):  
Lori M. Hansen ◽  
Jay V. Solnick
Keyword(s):  
Helicobacter Pylori ◽  
Rhesus Monkey ◽  
Macaca Mulatta ◽  
Rhesus Monkeys ◽  
Urease Activity ◽  
Rhesus Macaques ◽  
Selection For ◽  
H Pylori ◽  
Selection Of

ABSTRACT Helicobacter pylori strain J166 recovered from experimentally inoculated rhesus monkeys had up to a 250-fold-increased urease activity over that before inoculation. This was found to result from the selection of urease positive J166 clones from a heterogenous inoculum, which was predominantly urease negative due to a 1-bp insertion in the ureA gene. These results confirm the importance of urease for H. pylori colonization. Strain J166 is particularly well adapted to the rhesus monkey, since it colonized preferentially despite the fact that less than 0.1% of the inoculum was urease positive.

scholarly journals The Novel Helicobacter pylori CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance,Urease Modulation, and Gastric Colonization

2006 ◽  
Vol 74 (7) ◽  
pp. 3845-3852 ◽  
Author(s):  
Frank Nils Stähler ◽  
Stefan Odenbreit ◽  
Rainer Haas ◽  
Julia Wilrich ◽  
Arnoud H. M. Van Vliet ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Metal Ion ◽  
Insertional Mutagenesis ◽  
Urease Activity ◽  
Ion Homeostasis ◽  
Metal Ion Homeostasis ◽  
Gastric Colonization ◽  
Nickel Homeostasis ◽  
H Pylori ◽  
Cadmium Zinc

ABSTRACT Maintaining metal homeostasis is crucial for the adaptation of Helicobacter pylori to the gastric environment. Iron, copper, and nickel homeostasis has recently been demonstrated to be required for the establishment of H. pylori infection in animal models. Here we demonstrate that the HP0969-0971 gene cluster encoding the Czc-type metal export pump homologs HP0969, HP0970, and the H. pylori-specific protein HP0971 forms part of a novel H. pylori metal resistance determinant, which is required for gastric colonization and for the modulation of urease activity. Insertional mutagenesis of the HP0971, HP0970, or HP0969 genes in H. pylori reference strain 26695 resulted in increased sensitivity to cadmium, zinc, and nickel (czn), suggesting that the encoded proteins constitute a metal-specific export pump. Accordingly, the genes were designated cznC (HP0971), cznB (HP0970), and cznA (HP0969). The CznC and CznA proteins play a predominant role in nickel homeostasis, since only the cznC and cznA mutants but not the cznB mutant displayed an 8- to 10-fold increase in urease activity. Nickel-specific affinity chromatography demonstrated that recombinant versions of CznC and CznB can bind to nickel and that the purified CznB protein interacted with cadmium and zinc, since both metals competitively inhibited nickel binding. Finally, single cznA, cznB, and cznC mutants did not colonize the stomach in a Mongolian gerbil-based animal model. This demonstrates that the metal export functions of H. pylori cznABC are essential for gastric colonization and underlines the extraordinary importance of metal ion homeostasis for the survival of H. pylori in the gastric environment.

scholarly journals Helicobacter pylori Containing Only Cytoplasmic Urease Is Susceptible to Acid

1998 ◽  
Vol 66 (11) ◽  
pp. 5060-5066 ◽  
Author(s):  
Partha Krishnamurthy ◽  
Mary Parlow ◽  
Jason B. Zitzer ◽  
Nimish B. Vakil ◽  
Harry L. T. Mobley ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Urease Activity ◽  
Acid Resistance ◽  
Etiologic Agent ◽  
Stationary Phase Culture ◽  
Colonization Factor ◽  
Acid Environment ◽  
H Pylori

ABSTRACT Helicobacter pylori, an important etiologic agent in a variety of gastroduodenal diseases, produces large amounts of urease as an essential colonization factor. We have demonstrated previously that urease is located within the cytoplasm and on the surface of H. pylori both in vivo and in stationary-phase culture. The purpose of the present study was to assess the relative contributions of cytoplasmic and surface-localized urease to the ability of H. pylori to survive exposure to acid in the presence of urea. Toward this end, we compared the acid resistance in vitro of H. pylori cells which possessed only cytoplasmic urease to that of bacteria which possessed both cytoplasmic and surface-localized or extracellular urease. Bacteria with only cytoplasmic urease activity were generated by using freshly subcultured bacteria or by treating repeatedly subcultured H. pylori with flurofamide (1 μM), a potent, but poorly diffusible urease inhibitor. H. pyloriwith cytoplasmic and surface-located urease activity survived in an acid environment when 5 mM urea was present. In contrast, H. pylori with only cytoplasmic urease shows significantly reduced survival when exposed to acid in the presence of 5 mM urea. Similarly,Escherichia coli SE5000 expressing H. pyloriurease and the Ni2+ transport protein NixA, which expresses cytoplasmic urease activity at levels similar to those in wild-typeH. pylori, survived minimally when exposed to acid in the presence of 5 to 50 mM urea. We conclude that cytoplasmic urease activity alone is not sufficient (although cytoplasmic urease activity is likely to be necessary) to allow survival of H. pyloriin acid; the activity of surface-localized urease is essential for resistance of H. pylori to acid under the assay conditions used. Therefore, the mechanism whereby urease becomes associated with the surface of H. pylori, which involves release of the enzyme from bacteria due to autolysis followed by adsorption of the enzyme to the surface of intact bacteria (“altruistic autolysis”), is essential for survival of H. pylori in an acid environment. The ability of H. pylori to survive exposure to low pH is likely to depend on a combination of both cytoplasmic and surface-associated urease activities.

scholarly journals The Helicobacter pylori UreI Protein Is Not Involved in Urease Activity but Is Essential for Bacterial Survival In Vivo

1998 ◽  
Vol 66 (9) ◽  
pp. 4517-4521 ◽  
Author(s):  
Stéphane Skouloubris ◽  
Jean-Michel Thiberge ◽  
Agnès Labigne ◽  
Hilde De Reuse
Keyword(s):  
Helicobacter Pylori ◽  
Urease Activity ◽  
Saline Solution ◽  
Integral Membrane Protein ◽  
Bacterial Survival ◽  
Acidic Conditions ◽  
H Pylori ◽  
Phosphate Buffered Saline

ABSTRACT We produced defined isogenic Helicobacter pylori ureImutants to investigate the function of UreI, the product of one of the genes of the urease cluster. The insertion of a catcassette had a strong polar effect on the expression of the downstream urease genes, resulting in very weak urease activity. Urease activity, measured in vitro, was normal in a strain in which ureI was almost completely deleted and replaced with a nonpolar cassette. In contrast to previous reports, we thus found that the product ofureI was not necessary for the synthesis of active urease. Experiments with the mouse-adapted H. pylori SS1 strain carrying the nonpolar ureI deletion showed that UreI is essential for H. pylori survival in vivo and/or colonization of the mouse stomach. The replacement of ureIwith the nonpolar cassette strongly reduced H. pylorisurvival in acidic conditions (1-h incubation in phosphate-buffered saline solution at pH 2.2) in the presence of 10 mM urea. UreI is predicted to be an integral membrane protein and may therefore be involved in a transport process essential for H. pylori survival in vivo.

scholarly journals Isolation of Helicobacter pylori Genes That Modulate Urease Activity

1999 ◽  
Vol 181 (8) ◽  
pp. 2477-2484 ◽  
Author(s):  
David J. McGee ◽  
Carrie A. May ◽  
Rachel M. Garner ◽  
Janette M. Himpsl ◽  
Harry L. T. Mobley
Keyword(s):  
Helicobacter Pylori ◽  
Pathogenic Bacteria ◽  
Urease Activity ◽  
Regulatory Gene ◽  
Dna Helicase ◽  
E Coli ◽  
Dna Library ◽  
Flagellar Biosynthesis ◽  
H Pylori ◽  
High Level

ABSTRACT Helicobacter pylori urease, a nickel-requiring metalloenzyme, hydrolyzes urea to NH3 and CO2. We sought to identify H. pylori genes that modulate urease activity by constructing pHP8080, a plasmid which encodes both H. pylori urease and the NixA nickel transporter. Escherichia coli SE5000 and DH5α transformed with pHP8080 resulted in a high-level urease producer and a low-level urease producer, respectively. An H. pylori DNA library was cotransformed into SE5000 (pHP8080) and DH5α (pHP8080) and was screened for cotransformants expressing either lowered or heightened urease activity, respectively. Among the clones carrying urease-enhancing factors, 21 of 23 contained hp0548, a gene that potentially encodes a DNA helicase found within the cag pathogenicity island, and hp0511, a gene that potentially encodes a lipoprotein. Each of these genes, when subcloned, conferred a urease-enhancing activity in E. coli (pHP8080) compared with the vector control. Among clones carrying urease-decreasing factors, 11 of 13 clones contained the flbA (also known asflhA) flagellar biosynthesis/regulatory gene (hp1041), an lcrD homolog. The LcrD protein family is involved in type III secretion and flagellar secretion in pathogenic bacteria. Almost no urease activity was detected in E. coli (pHP8080) containing the subcloned flbA gene. Furthermore, there was significantly reduced synthesis of the urease structural subunits in E. coli (pHP8080) containing the flbA gene, as determined by Western blot analysis with UreA and UreB antiserum. Thus, flagellar biosynthesis and urease activity may be linked in H. pylori. These results suggest that H. pylori genes may modulate urease activity.

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